The long-term objective of the research proposed is to develop a transmucosal delivery technology which will eliminate the necessity for the parenteral administration of protein and peptide drugs. The goals of the phase I program are to synthesize, physically characterize and evaluate in an animal model a novel class of membrane permeation enhancers based on the fusidic acid nucleus. The novel compounds are meant to complement and improve upon California Biotechnology's proprietary enhancer, sodium taurodihydrofusidate. The synthesis of these compounds will be carried out using conventional synthetic procedures the C-21 carboxylate of the fusidic acid nucleus will be converted to an anhydride and then reacted with the desired molecule to give an amide linked fusidate derivative. The CMC, CMT and the pKa of each enhancer molecule will be determined. Using insulin and beta- interferon as model proteins, the ability of these molecules to enhance absorption across the nasal mucosa will be evaluated in a rat model. The widespread use of proteins and peptides as therapeutics is dependent on finding an alternate to parenteral administration. The potential market for effective, non-toxic permeation enhancers is expected to be enormous.